The proposed study will investigate the electron transfer pathways in liver microsomes from reduced pyridine nucleotides through NADPH- cytochrome c reductase or NADH-cytochrome b5 reductase and cytochrome b5 to each of three terminal oxidases, the microsomal mixed function oxidase, the fatty acyl CoA desaturase and the lipid peroxidase, in order to determine what directs the flow of electrons to each oxidase. The levels of the terminal enzymes will be modifid by different conditions in vivo (starvation, high carbohydrate diets or phenobarbital administration), and electron transfer component levels will be modified by fortification with purified enzymes or by addition of their specific antibodies. Induction of a new low spin type of cytochrome P-450 by PCN, a new type of inducer, will be accomplished, and the characteristics of this enzyme will be determined (substrate specificity, spectrum, binding spectra of drugs, ESR spectrum and the appropriate kinetic constant). Other studies planned include determination of the manner in which the antifungal agent, griseofulvin, causes hepatic necrosis in mice; the role of lipid peroxidase in the damage is being investigated.